The goals of the Program Project are to: (1) elucidate the factors determining nitrogen wastage during restricted nitrogen intake in normals and in patients with diseases characterized by impaired mechanisms for nitrogen disposal, and (2) to determine how nitrogen-free analogues of essential amino acids may be used advantageously to improve nitrogen conservation under these conditions. During the coming year, we plan to pursue three lines of inquiry. First, we propose to study ornithine-deficient cats, in an effort to determine the role of impaired ornithine disposal in the hyperammonemia of organic acidemias. Preliminary studies have indicated that ornithine synthesis is severely impaired in the organic acid loaded rat. Second, therapy of portal-systemic encephalopathy with ornithine salts of branched-chain ketoacids will be extended to children. During the past year, we demonstrated that these compounds improve portal-systemic encephalopathy more than their components and more than branched-chain amino acids at twice the molar dose, and obtained preliminary results indicating that they improve protein tolerance as well. Finally, efforts to improve the palatability and to optimize the dosage and dosage form of the mixture of essential amino acids and their nitrogen-free analogues used for the treatment of patients with chronic renal failure will continue, using an animal model of renal insufficiency developed during the past year as well as long-term clinical studies.